Antibacterial triterpenoids from Dillenia papuana and their structure-activity relationships

Two new oleanene-type triterpenoids, dillenic acids D and E, have been isolated from the leaves and stems of Dillenia papuana together with the new natural product 3-oxoolean-12-en-30-oic acid. Together with these compounds, the known compound, betulinic acid (3β-hydroxy-20(29)-lupen-28-oic acid) was isolated as the major component of the fractions studied. Dillenic acids D and E were characterized as 2,3-seco-2-oxoolean-12-en-3-methylester-30-oic acid and 1,3β-dihydroxyolean-12-en-30-oic acid and their nuclear magnetic resonance data were unambiguously assigned using two-dimensional nuclear magnetic resonance techniques. A comparison of antibacterial activities of these compounds with the earlier reported dillenic acids A-C indicated that, aside from a double bond in γ- or δ-position to a carboxylic group, a ketone function in ring A of an oleanene-skeleton may be required for the observed activity.     

The role of spartin and its novel ubiquitin binding region in DALIS occurrence

Troyer syndrome is an autosomal recessive hereditary spastic paraplegia (HSP) caused by frameshift mutations in the SPG20 gene that results in a lack of expression of the truncated protein. Spartin is a multifunctional protein, yet only two conserved domains—a microtubule-interacting and trafficking domain and a plant-related senescence domain involved in cytokinesis and mitochondrial physiology, respectively—have been defined. We have shown that overexpressed spartin binds to the Ile44 hydrophobic pocket of ubiquitin, suggesting spartin might contain a ubiquitin-binding domain. In the present study, we demonstrate that spartin contributes to the formation of dendritic aggresome-like induced structures (DALIS) through a unique ubiquitin-binding region (UBR). Using short hairpin RNA, we knocked down spartin in RAW264.7 cells and found that DALIS frequency decreased; conversely, overexpression of spartin increased the percentage of cells containing DALIS. Using nuclear magnetic resonance spectroscopy, we characterized spartin''s UBR and defined the UBR''s amino acids that are key for ubiquitin binding. We also found that spartin, via the UBR, binds Lys-63–linked ubiquitin chains but does not bind Lys-48–linked ubiquitin chains. Finally, we demonstrate that spartin''s role in DALIS formation depends on key residues within its UBR.     

Chemotaxis of cholera vibrios: a study method and the relation to different substances

The chemotaxis of V. cholerae in response to 56 different substances (amino acids, carbohydrates, salts, etc.) has been studied by the methods of visual observation and quantitative determination. Attractants, neutral substances and one repellent have been revealed. Adler's method (1973) has been modified with regard to the requirements for the working procedures in handling the causative agents of highly dangerous infections.     

New method for the histochemical demonstration of dipeptidyl aminopeptidase I activity using a novel anthraquinoyl hydrazide substrate.

A new method for the histochemical localization of dipeptidyl aminopeptidase I (DPP I, cathepsin C), based on a newly synthesized substrate-Gly-L-Phe-5-chloro-1-anthraquinoyl hydrazide.HCl (Gly-Phe-CAH), is proposed. The enzyme activity liberates 5-chloro-1-anthraquinoyl hydrazine (CAH)--a water-insoluble brown-reddish compound, which precipitates on the enzyme locations. The primary reaction product reacts simultaneously or, otherwise, by post-coupling with p-anisaldehyde (p-AA), thus converting to the reddish-violet amorphous hydrazone--the final reaction product. The validity of enzyme localization is thus assured by the insolubility of the primary reaction product and does not depend on the rate of the second reaction step. The enzyme studied is successfully localized in different rat organs using the newly proposed technique.     

Decrease of dehydrogenase activity of cerebral glyceraldehyde-3-phosphate dehydrogenase in different animal models of Alzheimer's disease

Recently, a relationship between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the β-amyloid precursor protein (βAPP) in relationship with the pathogenesis of Alzheimer's disease (AD) has been suggested. Therefore, we studied the specific activity of GAPDH in the different animal models of AD: transgenic mice (Tg2576) and rats treated with β-amyloid, or thiorphan, or lipopolysaccharides (LPS) and interferon γ (INFγ). We observed that GAPDH activity was significantly decreased in the brain samples from TG mice. The injection of β-amyloid, or thiorphan, an inhibitor of neprilysin involved in β-amyloid catabolism, in rat brains resulted in a pronounced reduction of the enzyme activity. The infusion of LPS and IFNγ, which can influence the progression of the AD, significantly reduced the enzyme activity.